Dual Requirement for Yeast hnRNP Nab2p in mRNA poly(A) Tail Length Control and Nuclear Export

Recent studies of mRNA export factors have provided additional evidence for a mechanistic link between mRNA 3′‐end formation and nuclear export. Here, we identify Nab2p as a nuclear poly(A)‐binding protein required for both poly(A) tail length control and nuclear export of mRNA. Loss of NAB2 expression leads to hyperadenylation and nuclear accumulation of poly(A)+ RNA but, in contrast to mRNA export mutants, these defects can be uncoupled in a nab2 mutant strain. Previous studies have implicated the cytoplasmic poly(A) tail‐binding protein Pab1p in poly(A) tail length control during polyadenylation. Although cells are viable in the absence of NAB2 expression when PAB1 is overexpressed, Pab1p fails to resolve the nab2Δ hyperadenylation defect even when Pab1p is tagged with a nuclear localization sequence and targeted to the nucleus. These results indicate that Nab2p is essential for poly(A) tail length control in vivo, and we demonstrate that Nab2p activates polyadenylation, while inhibiting hyperadenylation, in the absence of Pab1p in vitro. We propose that Nab2p provides an important link between the termination of mRNA polyadenylation and nuclear export

The hRPC62 subunit of human RNA polymerase III displays helicase activity.

In Eukaryotes, tRNAs, 5S RNA and U6 RNA are transcribed by RNA polymerase (Pol) III. Human Pol III is composed of 17 subunits. Three specific Pol III subunits form a stable ternary subcomplex (RPC62-RPC39-RPC32α/β) being involved in pre-initiation complex formation. No paralogues for subunits of this subcomplex subunits have been found in Pols I or II, but hRPC62 was shown to be structurally related to the general Pol II transcription factor hTFIIEα. Here we show that these structural homologies extend to functional similarities. hRPC62 as well as hTFIIEα possess intrinsic ATP-dependent 3'-5' DNA unwinding activity. The ATPase activities of both proteins are stimulated by single-stranded DNA. Moreover, the eWH domain of hTFIIEα can replace the first eWH (eWH1) domain of hRPC62 in ATPase and DNA unwinding assays. Our results identify intrinsic enzymatic activities in hRPC62 and hTFIIEα

The lavender plumage colour in Japanese quail is associated with a complex mutation in the region of MLPH that is related to differences in growth, feed consumption and body temperature

Background The lavender phenotype in quail is a dilution of both eumelanin and phaeomelanin in feathers that produces a blue-grey colour on a wild-type feather pattern background. It has been previously demonstrated by intergeneric hybridization that the lavender mutation in quail is homologous to the same phenotype in chicken, which is caused by a single base-pair change in exon 1 of MLPH. Results In this study, we have shown that a mutation of MLPH is also associated with feather colour dilution in quail, but that the mutational event is extremely different. In this species, the lavender phenotype is associated with a non-lethal complex mutation involving three consecutive overlapping chromosomal changes (two inversions and one deletion) that have consequences on the genomic organization of four genes (MLPH and the neighbouring PRLH, RAB17 and LRRFIP1). The deletion of PRLH has no effect on the level of circulating prolactin. Lavender birds have lighter body weight, lower body temperature and increased feed consumption and residual feed intake than wild-type plumage quail, indicating that this complex mutation is affecting the metabolism and the regulation of homeothermy. Conclusions An extensive overlapping chromosome rearrangement was associated with a non-pathological Mendelian trait and minor, non deleterious effects in the lavender Japanese quail which is a natural knockout for PRLH

Геологическое строение, нефтегазоносность и подсчет запасов газа пласта ПК1 Антипаютинского газового месторождения (ЯНАО)

На основе комплексной интерпретации данных сейсморазведки 3D, данных ГИС и испытания пласта в разведочных скважинах обосновано геологическое строение газовой залежи пласта ПК1 Антипаютинского месторождения. Проведен обобщающий анализ результатов лабораторных исследований кернов, пластовых флюидов, промыслово-геофизических и газогидродинамических исследований изучаемого объекта. Построены карты кровли коллекторов пласта ПК1, поверхности межфлюидного контакта, эффективных газонасыщенных толщин пласта. Дано обоснование подсчётных параметров, определяемых по данным ГИС (коэффициенты пористости, газонасыщенности, эффективные газонасыщенные толщины). На основе построенной детальной геологической модели проведён дифференцированный подсчёт запасов газа.On the basis of complex interpretation this seismic exploration 3D, data of GIS and test of layer in prospecting wells the geological structure of a gas deposit of PK1 layer of the Antipayutinsky field is proved. The generalizing analysis of results of laboratory researches of cores, formation fluids, trade and geophysical and gas-hydrodynamic researches of the studied object is carried out. Cards of a roof of collectors of PK1 layer, a surface of interfluid contact, effective gas-saturated thickness of layer are constructed. Justification of the subcalculating parameters determined by data of GIS (coefficients of porosity, gas saturation, effective gas-saturated thickness) is given. On the basis of the constructed detailed geological model the differentiated calculation of reserves of ga

The "silver" Japanese quail and the MITF gene: causal mutation, associated traits and homology with the "blue" chicken plumage

<p>Abstract</p> <p>Background</p> <p>The <it>MITF </it>(<it>microphthalmia-associated transcription factor</it>) gene has been investigated in mice and various vertebrates but its variations and associated effects have not yet been explored much in birds. The present study describes the causal mutation <it>B </it>at the <it>MITF </it>gene responsible for the "silver" plumage colour in the Japanese quail (<it>Coturnix japonica</it>), and its associated effects on growth and body composition, and tests its allelism with the "blue" plumage colour mutation <it>Bl </it>in <it>Gallus gallus</it>.</p> <p>Results</p> <p>The semi dominant <it>B </it>mutation results from a premature stop codon caused by a 2 bp deletion in exon 11 of <it>MITF</it>. Homozygous "white" (<it>B/B</it>) quail which have a white plumage also show a slightly lower growth, lower body temperature, smaller heart, and lighter <it>pectoralis </it>muscles but more abdominal adipose tissue than the recessive homozygous "wild-type" (<it>+/+</it>) and heterozygous "silver" (<it>B/+</it>) quail. Similar observations on cardiac and body growth were made on mice (<it>Mus musculus</it>) homozygous for mutations at <it>MITF</it>. The production of chicken-quail hybrids with a white plumage obtained by crossing <it>Bl/+ </it>chicken heterozygous for the <it>blue </it>mutation with <it>B/B </it>white quail indicated that the mutations were allelic.</p> <p>Conclusion</p> <p>The "silver" Japanese quail is an interesting model for the comparative study of the effects of <it>MITF </it>in birds and mammals. Further investigation using a chicken family segregating for the "blue" plumage and molecular data will be needed to confirm if the "blue" plumage in chicken results from a mutation in <it>MITF</it>.</p

Parasitosis intestinales y factores ambientales en una población rural de Argentina, 2002-2003

We evaluate the prevalence of intestinal parasites in 504 people and the degree of association between environmental variables and parasites found in population, soil and water in a rural area of Argentina during 2002-2003. A structured survey was used to evaluate the environmental variables and fecal-human, soil and water samples were analyzed. The prevalence of parasites was 45.4%. Most prevalent protozoa were Blastocystis hominis (27.2%) and Giardia lamblia (6.9%), while the most prevalent helminth was Ascaris lumbricoides (3.8%). The analyzed environmental variables showing association (p < 0.05) with presence of parasites in population were: cardboard-tin or wooden house, dirt floor, home or communal water pump, faucet outside the house or public faucet and cesspool or latrine. Parasite forms were found in 82.3% of the soil samples and in 84.2% of the water samples. In both samples we found parasites that were also found in people. In this study we have found deficient sanitary conditions associated with presence of parasites in population and we have evidenced that contaminated soil and water were the source of these parasites.Hemos evaluado la prevalencia de parásitos intestinales en 504 personas y el grado de asociación entre las variables ambientales y los parásitos intestinales hallados en la población, el suelo y el agua de una zona rural de Argentina durante 2002-2003. Se utilizó una encuesta estructurada para relevar las variables ambientales y se examinaron muestras fecales humanas, de agua y de suelo. La prevalencia parasitaria fue de 45,4%. Los protozoos prevalentes fueron Blastocystis hominis (27,2%) y Giardia lamblia (6,9%), mientras que el helminto mas prevalente fue Ascaris lumbricoides (3,8%). Las variables ambientales analizadas que mostraron asociación (p < 0,05) con la presencia de parásitos en la población fueron: casa de cartón-chapa o de madera con piso de tierra, bomba de agua domiciliaria o comunitaria, canilla fuera de la casa o pública y pozo ciego o letrina. Elementos parasitarios fueron hallados en el 82,3% de las muestras de suelo y en el 84,2% de las muestras de agua. En ambas muestras fueron hallados parásitos que también se encontraron en las personas. En este trabajo hemos hallado deficientes condiciones sanitarias asociadas con la presencia de parásitos en las personas y hemos evidenciado que el suelo y el agua contaminada fueron la fuente de esos parasitos

Alternative 3′ Pre-mRNA Processing in Saccharomyces cerevisiae Is Modulated by Nab4/Hrp1 In Vivo

The Saccharomyces cerevisiae RNA-binding protein Nab4/Hrp1 is a component of the cleavage factor complex required for 3′ pre-mRNA processing. Although the precise role of Nab4/Hrp1 remains unclear, it has been implicated in correct positioning of the cleavage site in vitro. Here, we show that mutation or overexpression of NAB4/HRP1 alters polyA cleavage site selection in vivo. Using bioinformatic analysis, we identified four related motifs that are statistically enriched in Nab4-associated transcripts; each motif is similar to the known binding site for Nab4/Hrp1. Site-directed mutations in predicted Nab4/Hrp1 binding elements result in decreased use of adjacent cleavage sites. Additionally, we show that the nab4-7 mutant displays a striking resistance to toxicity from excess copper. We identify a novel target of alternative 3′ pre-mRNA processing, CTR2, and demonstrate that CTR2 is required for the copper resistance phenotype in the nab4-7 strain. We propose that alternative 3′ pre-mRNA processing is mediated by a Nab4-based mechanism and that these alternative processing events could help control gene expression as part of a physiological response in S. cerevisiae

A DNA target-enrichment approach to detect mutations, copy number changes and immunoglobulin translocations in multiple myeloma.

Genomic lesions are not investigated during routine diagnostic workup for multiple myeloma (MM). Cytogenetic studies are performed to assess prognosis but with limited impact on therapeutic decisions. Recently, several recurrently mutated genes have been described, but their clinical value remains to be defined. Therefore, clinical-grade strategies to investigate the genomic landscape of myeloma samples are needed to integrate new and old prognostic markers. We developed a target-enrichment strategy followed by next-generation sequencing (NGS) to streamline simultaneous analysis of gene mutations, copy number changes and immunoglobulin heavy chain (IGH) translocations in MM in a high-throughput manner, and validated it in a panel of cell lines. We identified 548 likely oncogenic mutations in 182 genes. By integrating published data sets of NGS in MM, we retrieved a list of genes with significant relevance to myeloma and found that the mutational spectrum of primary samples and MM cell lines is partially overlapping. Gains and losses of chromosomes, chromosomal segments and gene loci were identified with accuracy comparable to conventional arrays, allowing identification of lesions with known prognostic significance. Furthermore, we identified IGH translocations with high positive and negative predictive value. Our approach could allow the identification of novel biomarkers with clinical relevance in myeloma

¿Esperamos los síntomas/signos para solicitar un análisis parasitológico?

Las parasitosis intestinales se presentan con mayor frecuencia en población pediátrica. Generalmente los profesionales solicitan un análisis parasitológico cuando detectan algún síntoma/signo (S/S) que despierta la sospecha. Otra alternativa de muchos pediatras es la desparasitación de los niños sin solicitar el correspondiente análisis parasitológico; conducta que impide conocer las especies prevalentes de cada región y además, conlleva el riesgo de desarrollar resistencia a los antiparasitarios.Facultad de Ciencias Médica